tbuckley/cabot-search huggingface dataset:
Darolutamide observational (DAROL) study in patients with nonmetastatic castration-resistant prostate cancer: Second interim analysis.
Authors: Evan Y. Yu, Christopher Michael Pieczonka, Hiroyoshi Suzuki, James L. Bailen, Geoffrey T. Gotto, Joelle P. Hamilton, Hiroji Uemura, Declan G. Murphy, Thierry Lebret, Murilo de Almeida Luz, Jorge A. Ortiz, Patrick Adorjan, Javeed Khan, Alberto Briganti, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2023)

e17095 Background: In ARAMIS (NCT02200614), darolutamide (DARO) significantly improved metastasis-free survival (MFS) by ~2 years (HR 0.41, 95% CI 0.34–0.50) and reduced the risk of death by 31% (HR 0.69, 95% CI 0.53–0.88) compared with placebo in men with nonmetastatic castration-resistant prostate cancer (nmCRPC), with a favorable tolerability profile. The ongoing DAROL study (NCT04122976) aims to understand the real-world safety and effectiveness of DARO in patients (pts) with nmCRPC. We report results from the pre-planned second interim analysis (IA). Methods: DAROL is a global, open-label, single-arm, non-interventional study in pts aged ≥18 years with confirmed nmCRPC for whom the decision to be treated with DARO is decided pre-enrollment. The primary endpoint is safety, including incidence, severity, and frequency of treatment-emergent adverse events (TEAEs). Secondary endpoints are patient demographics and disease characteristics, treatment duration, MFS, overall survival (OS), time to prostate-specific antigen (PSA) progression, and PSA response. Primary and secondary endpoints are reported after 300 pts completed ≥6 mo of treatment. All treated pts were assessed for safety while efficacy was evaluated in pts who did not violate any eligibility criteria and had ≥1 post-baseline assessment (cut-off October 11, 2022). Results: Of the 300 treated pts, the percentage enrolled in North America/Europe/Asia Pacific/Latin America was 45%/30%/25%/ &lt; 1%, respectively. Median age was 80 years; 51% had a reported Gleason score &gt; 7; 92% had a reported ECOG performance status of 0/1. Median baseline (BL) PSA was 3.9 ng/mL (range 0–248.0), with 21% of pts reporting PSA &lt; 2 ng/mL. Median BL PSA doubling time (PSADT) was 5.3 mo (range 0–36.2), with 42% of pts reporting PSADT &gt; 6 mo. At the data cut-off, median follow-up time was 14.8 mo (interquartile range [IQR] 10.9–19.3) and median treatment duration was 13.4 mo (IQR 9.3–17.8). The incidences of TEAEs and DARO-related TEAEs were generally low (Table), consistent with the safety profile of DARO reported in ARAMIS. Fatigue occurred in ≥5% of pts. For the 263 pts eligible for efficacy analysis, median time to PSA progression was 17.6 mo (95% CI 13.2–19.0); MFS/OS data remain immature. PSA declines from baseline of ≥30%, ≥50%, and ≥90% at any time were observed in 80%, 76%, and 54% of pts, respectively. Conclusions: In the DAROL second IA, under real-world conditions, DARO continued to show a favorable safety profile, consistent with the clinical profile of ARAMIS, with no new safety signals. Clinical trial information: NCT04122976 . [Table: see text]
Busulfan versus treosulfan conditioning for acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis.
Authors: Mohammad Ebad Ur Rehman, Mahammed Khan suheb, Haddaya Umar, Fnu Farheen Naaz, Zunairah Shah, Zarak Khan, Huzaifa Ahmad Cheema, Jawad Basit, Faizan Fazal, Shahzaib Maqbool, Muhammed Farhan, Kuldeep Dhama, Usman Ali Akbar, Raheel Iftikhar, Ahmad Iftikhar, Faiz Anwer
Journal: Journal of Clinical Oncology (2023)

e19032 Background: Busulfan containing myeloablative conditioning regimens are widely used before allogeneic hematological stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Treosulfan-based conditioning regimens are a potential alternative with potent myelotoxic immunosuppressive characteristics and favorable extramedullary toxicity profile compared to busulfan. In order to determine the optimal conditioning regimen, we conducted a systematic review and meta-analysis to compare the efficacy and safety outcomes of busulfan and treosulfan based conditioning regimens in patients with AML/MDS. Methods: A retrospective systematic literature search was undertaken on PubMed, Cochrane, Embase and Clinicaltrials.gov, using MeSH terms and relevant keywords for AML, MDS, busulfan and treosulfan, to retrieve studies published prior to February 5, 2023. Efficacy outcomes were overall survival (OS), disease-free survival (DFS), and relapse. Safety outcomes included non-relapse mortality (NRM), acute (a) and chronic (c) graft-versus-host disease (GvHD). The random-effects model with the Mantel-Haenszel method was used to pool risk ratios (RR) for dichotomous variables in Revman version 5.4. Results: The initial search retrieved 1094 articles. After removal of duplicates, reviews and non-relevant articles, data was extracted from seven different studies. Busulfan and treosulfan were employed in 4706 and 1979 patients, respectively. The median age ranged from 55 to 61 years, and the median follow-up ranged from 14 to 58 months. The treosulfan and busulfan doses administered ranged from 10-42 g/m2 and 0.8-12.8 mg/kg, respectively. Treosulfan was superior to busulfan in terms of OS (RR 1.39, 95% CI 1.15-1.68, p-value 0.0007, I2 58%), DFS (RR 1.39, 95% CI 1.10-1.75, p-value 0.006, I2 60%) and NRM (RR 0.95, 95% CI 0.90-1.00, p-value 0.05, I2 67%). The two regimens were comparable in terms of relapse (RR 0.96, 95% CI 0.89-1.04, p-value 0.33, I2 76%), aGvHD (RR 1.00, 95% CI 0.65-1.54, p-value 1.00, I2 94%) and cGvHD (RR 1.00, 95% CI 0.95-1.05, p-value 0.92, I2 0%). Conclusions: Treosulfan was superior in terms of OS, EFS and NRM, whereas both regimens were comparable in terms of relapse, aGvHD and cGvHD. Treosulfan may be more favorable compared to busulfan as conditioning in AML/MDS. Large scale prospective studies are needed to confirm the most suitable option.
Final survival analysis of the phase III OVHIPEC-1 trial of hyperthermic intraperitoneal chemotherapy in ovarian cancer after ten year follow-up.
Authors: Lot Aronson, Marta I. Lopez-Yurda, Simone N Koole, Jules H Schagen van Leeuwen, Henk Schreuder, Ralph Hermans, Ignace H.J.T. de Hingh, Mignon D.J.M. Van Gent, Henriëtte J.G. Arts, Maaike van Ham, Peter Van Dam, Peter Vuylsteke, Arend Aalbers, Victor Verwaal, Koen Van de Vijver, Neil K Aaronson, Gabe S. Sonke, Willemien Van Driel
Journal: Journal of Clinical Oncology (2023)

5509 Background: The randomized, phase 3 OVHIPEC-1 trial (NCT00426257) investigated the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. OVHIPEC-1 previously demonstrated improved recurrence-free and overall survival after 4.7 years of follow-up. Here, we report the final survival outcomes after ten years of follow-up. In addition, we report new data on the subsequent anti-cancer treatments given after disease progression. Methods: Patients were randomized to receive interval cytoreductive surgery with or without HIPEC, after receiving three cycles of neo-adjuvant carboplatin and paclitaxel. Randomization was performed at the time of surgery when either complete (no visible disease) or optimal cytoreduction (residual tumor measuring &lt;10mm in diameter) was anticipated. All patients received an additional three cycles of adjuvant systemic chemotherapy. We analyzed survival according to the intention-to-treat principle using stratified log-rank tests and Kaplan-Meier methods. Subsequent lines of therapy were compared between arms. Results: At a median follow-up of 10.1 years, 114 of 123 patients (92.7%) who underwent surgery alone and 109 of 122 patients (89.3%) who had surgery-plus-HIPEC experienced recurrence, progression, or death from any cause. Median recurrence-free survival was 10.7 months in the surgery group compared to 14.3 months in the surgery-plus-HIPEC group (HR, 0.63; 95% confidence interval [CI], 0.48-0.83; stratified P&lt;0.001). One hundred and eight patients (87.8%) in the surgery group have died as compared to 100 patients (82.0%) in the surgery-plus-HIPEC group. Median overall survival was 33.3 versus 44.9 months (HR, 0.70; 95% CI, 0.53-0.92; stratified P=0.011), respectively. Subsequent anti-cancer therapies, including chemotherapy (platinum and non-platinum based), secondary surgery, poly (ADP-ribose) polymerase (PARP) inhibitors and bevacizumab, were received by 104 patients (84.6%) in the surgery group and 100 patients (82.0%) in the surgery-plus-HIPEC group. The median number of subsequent systemic treatment lines was 2 (IQR 1-3) in both arms. Conclusions: This study provides the first long-term survival analysis of HIPEC in ovarian cancer and confirms the benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. No imbalance in subsequent therapy after disease recurrence was found that could explain the improved overall survival after HIPEC. Clinical trial information: NCT00426257 .
Biochemical recurrence (BCR) and outcomes in patients (pts) with prostate cancer (PC) following radical prostatectomy (RP).
Authors: Nasreen Khan, Rana R. McKay, Daniel Eidelberg Spratt, Niculae Constantinovici, Guifang Chen, Jorge A. Ortiz, Shankar Srinivasan, Zdravko Vassilev, Julie Xu, Neal D. Shore
Journal: Journal of Clinical Oncology (2023)

e17112 Background: RP is often the primary treatment option for pts with clinically localized PC. Despite its frequent success, more than 30% of pts eventually present with BCR, defined as detectable prostate-specific antigen (PSA) after RP. BCR is associated with a higher risk of developing distant metastasis and ultimately death. Current patterns of BCR and the impact of BCR on treatment choice and clinical outcomes are not well characterized. Methods: This retrospective cohort study uses nationally representative Optum © Electronic Medical Records (EMR) data from 1/2010 to 9/2021. Eligible pts were adults who underwent RP after PC diagnosis, had ≥ 3 available PSA values after RP, and had EMR activity for at least 6 mo before and 12 mo after RP. Pts with prior malignancy except nonmelanoma skin cancers and pts with metastatic PC at baseline (BL) or within 3 months after RP were excluded. The BL period was 6 mo before RP. Primary outcome was frequency of BCR (defined as PSA ≥ 0.2 ng/mL); secondary analyses included % of pts who progressed to metastasis, castration-resistant PC (CRPC), and death after BCR, and factors associated with time to BCR. Results: 15,198 pts who underwent RP were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 63.0 (36-88) y, 85.9% of pts were White, and 10.0% were African American. Median (Q1-Q3) follow-up was 3.9 (2.4-5.7) y, and 14.3% of pts had subsequent adjuvant/salvage radiation therapy (RT). Overall, 19.8% of all pts and 61.4% of the subgroup of 2,178 pts with subsequent RT developed BCR. Among pts with BCR (n = 3,016), 16.3% had a PSA doubling time ≤ 10 mo, 17.1% developed metastasis, 13.8% developed CRPC, and 9.7% died. In multivariate Cox regression models (Table), the BL factors associated with an increased risk of developing BCR were PSA 10- &lt; 20 or ≥ 20 ng/mL, Charlson comorbidity index (CCI) &gt; 0, age ≥ 65, African American race, public insurance, and living in the US South region. Conclusions: This real-world (RW) study evaluates the occurrence of BCR in pts who underwent RP with a curative intent from a large US database. This study confirms BL PSA as an important prognostic marker for BCR. A considerable % of pts with BCR developed metastatic PC (17%) or died (10%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC among pts with high-risk localized disease. [Table: see text]
Efficacy and safety of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer who had measurable residual disease: A post-hoc subgroup analysis of the PRIME study.
Authors: Beihua Kong, Lingying Wu, Jianqing Zhu, Rutie Yin, Jing Wang, Lingya Pan, Hong Zheng, Jihong Liu, Xiaohua Wu, Li Wang, Yi Huang, Ke Wang, Dongling Zou, Hongqin Zhao, Chunyan Wang, Weiguo Lu, An Lin, Xiaoa Zhen, Wenzhao Hang, Jianmei Hou
Journal: Journal of Clinical Oncology (2023)

5562 Background: Niraparib maintenance therapy significantly prolonged progression-free survival (PFS) versus placebo in patients with newly diagnosed advanced ovarian cancer (aOC), but its antitumor activity remains unclear in those with measurable residual disease (MRD) after first-line platinum-based chemotherapy (1LCT). This study aims to report the efficacy, including antitumor activity, and safety of niraparib maintenance therapy in patients with MRD after 1LCT from the phase 3 PRIME trial (NCT03709316). Methods: In PRIME, adults with newly diagnosed aOC who had received cytoreductive surgery and responded to 1LCT were randomized 2:1 to receive niraparib or placebo with stratification by receipt of neoadjuvant chemotherapy, response to 1LCT, status of germline BRCA mutations, and tumor homologous recombination deficiency status. Tumor assessment was conducted at baseline and every 12 weeks thereafter by blinded independent central review (BICR) according to RECIST, version 1.1. Between 29 June 2018 and 11 November 2019, 384 patients were randomized (255 niraparib, 129 placebo). The data cut-off date was 30 September 2021. This post-hoc analysis reports BICR-assessed objective response rate (ORR) and PFS in patients with MRD at baseline. An initial response was confirmed ≥4 weeks later. Results: In total, 73 (19.0%) patients (47 niraparib, 26 placebo) had MRD at baseline. Baseline characteristics were well balanced between the two MRD groups. Complete and partial responses, both confirmed, were observed in 12 (25.5%) and 15 (31.9%) niraparib-treated patients and 3 (11.5%) and 5 (19.2%) placebo-treated patients, respectively, leading to a confirmed ORR of 57.4% with niraparib and 30.8% with placebo (odds ratio, 3.20; 95% confidence interval [CI], 1.11–9.11). ORRs by biomarker status are provided in the table. Median PFS (95% CI) was 22.3 (8.7–not estimable) months with niraparib versus 8.3 (5.6–11.0) months with placebo (hazard ratio, 0.36; 95% CI, 0.19–0.71). Treatment-emergent adverse events (TEAEs) of grade ≥3 occurred in 28 (59.6%) niraparib-treated patients and 7 (26.9%) placebo-treated patients. TEAEs led to treatment discontinuation in three (6.4%) niraparib-treated patients and one (3.8%) placebo-treated patient. Conclusions: In patients with newly diagnosed aOC who had MRD after 1LCT, niraparib maintenance therapy tended to induce additional antitumor activity and led to a clinically meaningful increase in PFS versus placebo. Clinical trial information: NCT03709316 .[Table: see text]
Clinical outcomes of patients with cancer before the SARS COV2 pandemic vs during the pandemic: A nationwide analysis.
Authors: Siri Chandana Swarna, Vaishali Deenadayalan, Ali Shahbaz Shehbaz Baloch, Junglee Kim, Shweta Gupta
Journal: Journal of Clinical Oncology (2023)

e18569 Background: The novel SARS COV2 pandemic has disrupted cancer treatment, both preventive as well as treatment services. We aimed to study the clinical outcomes of cancer patients who were hospitalised before and during the pandemic. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2016-2020 was queried to identify adult patients (Age &gt; 18 years) with a diagnosis of cancer using the ICD-10 (International Classification of Diseases) codes. Study population was stratified based on the year of admission- 2016 to 2019 vs 2020 (the pandemic year). Primary outcomes included mortality, length of stay (LOS), and total hospitalization charges (THC). Secondary outcomes included prevalence of pulmonary embolism (PE), ICU admission, acute respiratory failure (ARF), blood transfusion, and sepsis. Statistics were performed using multivariate linear and logistic regression using STATA v17. Results: There were 18 million admissions in adults with cancer from 2016-2020. Among them 14.6 million (81.1%) were hospitalised during 2016-2019 (pre pandemic) whereas 3.4 million (18.9%) were hospitalized in 2020 (pandemic). There was no significant difference in the mean age of both groups, pandemic group had higher charlson comorbidity burden (66.4 vs 63.7%, p &lt; 0.01). Pandemic group had higher rates of DM (26 vs 24%), CHF (15 vs 13.8%), CKD (18 vs 16.5%), dyslipidemia (36.4 vs 33%), PEM (15 vs 13%), anemia (44 vs 42) all p &lt; 0.01. A total of 835,065 cancer patients died during the study period, the mortality rate in the pre-pandemic and pandemic years was 4.5% and 5% respectively (p &lt; 0.05). After adjusting for confounders, the all-cause mortality was increased in the pandemic group (aOR 1.10, 95% CI 1.05-1.12, p &lt; 0.01). The adjusted LOS was decreased by 0.1 days (95% CI: 0.06- 0.20, p &lt; 0.01)). The adjusted total hospitalization charges was increased by $12,891 (95% CI: 9745-16,035, p &lt; 0.01). Pandemic group had higher odds of sepsis (7.8 vs 6.5%), mechanical ventilation (4 vs 3%), pressor requirements (1.5 vs 1%), acute kidney injury (10 vs 7%) and acute respiratory failure (10 vs 7%), all p &lt; 0.01. Conclusions: During the COVID-19 pandemic, cancer patients with a high prevalence of medical comorbidities were more likely to be admitted to the hospital with COVID infection. The higher mortality in these patients was likely the result of higher secondary complications, also likely leading to earlier death explaining the lower LOS and higher hospitalization charges. Cancer patients with medical comorbidities should take higher preventive measures from COVID including encouraging continued primary vaccinations and regular boosters.
Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: A single-arm, phase II trial.
Authors: Wenjie Wu, Jie Yao, Tong Zhang, Jie Zhang
Journal: Journal of Clinical Oncology (2023)

e18072 Background: Previous studies confirmed locally advanced oral or oropharyngeal squamous cell carcinoma (LA OSCC or OPSCC) patients (pts) with a pathological response had higher probability of survival in neoadjuvant settings. Several ongoing trials of neoadjuvant immunotherapy in head and neck cancer showed promising results. However, the optimal regimen remains unclear. This trial aimed to evaluate the efficacy and safety of neoadjuvant therapy with anti-programmed cell death 1 (PD-1) mAb tislelizumab and chemotherapy, followed by surgery and adjuvant radiotherapy/chemoradiotherapy in LA OSCC or OPSCC. Methods: In this phase II, single-arm study, eligible pts aged 18-80 diagnosed with stage III-IV (AJCC v8) resectable or potentially resectable LA OSCC or OPSCC received neoadjuvant therapy with tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m 2 ), and cisplatin (60-75 mg/m 2 ) Q3W for 2 cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. The primary endpoint was major pathologic response (MPR). Secondary endpoints included pathological complete response (pCR), objective response rate (ORR), event-free survival (EFS), overall survival (OS) and safety. Results: Thirty-one pts were enrolled from Mar 2022 to Nov 2022, and completed neoadjuvant therapy, with an ORR of 61.3% (19/31) and CR rate of 6.5% (2/31). Of the 31 pts, 29 pts (18 OSCC, 13 OPSCC) successfully underwent surgery with a median age of 57 (34-72) yrs, smoking history 75.9%, alcohol history 72.4% and 82.8% of male. The clinical stage III, IVA and IVB accounted for 24.1%, 48.3% and 27.6%, respectively. The MPR rate was 65.5% (19/29), of which the pCR rate was 41.4% (12/29). R0 resection rate reached 100%. For the per-protocol population, 58.6% pts (17/29) complaint of symptoms included pain, trismus, dysphagic, and speech disorders, all of them reached remission after 2 cycles of neoadjuvant therapy. No delay of surgery occurred. Grade 3-4 adverse events (AEs) occurred in 3 pts including 3.4% G3 leukopenia, 6.9% G3 anemia and 3.4% G4 thrombocytopenia and mostly chemotherapy related. Grade 1-2 AEs included 13.8% anemia, 3.4% thrombocytopenia, 17.2% leukopenia, 13.8% increased aminotransferase, 3.4% increased creatinine, 3.4% hyperglycemia, 27.6% anorexia, 3.4% vomiting, 3.4% diarrhea, 10.3% constipation, 6.9% rash, 100% alopecia and 17.2% fatigue. Conclusions: Neoadjuvant tislelizumab combined with chemotherapy yielded promising MPR and pCR rates with an acceptable safety proﬁle in LA OSCC or OPSCC. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200056354 .
Retrospective review of 250 gallium-68 PSMA scans in prostate cancer patients in Health Canada Special Access Program.
Authors: Philip Frank Cohen, Robert Tarzwell, Jason Leong
Journal: Journal of Clinical Oncology (2023)

e17035 Background: Prostate Cancer is the most common malignancy in men, and until recently has been staged using standard imaging tests, such as ultrasound, CT, bone scan, and MRI. A novel imaging test targeting the membrane receptor, Prostate Specific Membrane Antigen (PSMA) using the PET tracer Ga-68 PSMA-11 has recently been approved in several countries for staging and assessing potential for radionuclide therapy. This agent was only recently approved in Canada, but has been available through the Health Canada Special Access (SA) Program for over a year, until it was approved (Illuccix, Telix Pharmaceuticals). Methods: In the past year, 275 prostate cancer patients were scanned at our facility (INITIO Medical Imaging, Burnaby BC) through Health Canada SA. All patients were required to have positive prostate cancer biopsies, with negative or indeterminate CT and bone scan, and rising PSA (prostate specific antigen) blood test in order to qualify for SA, or high risk Gleason Score prostate cancer. Results: Of the 275 patients, 71 had high risk cancers and 28/71 had positive PSMA studies (39%). 185 of the patients had biochemical evidence of recurrence and negative /indeterminate conventional imaging tests, and 101/185 or 55% had positive PSMA scans. All other patients were scanned for metastatic castrate resistant prostate cancer (MCRPC). Conclusions: Ga-68 PSMA scans are highly sensitive for upstaging patients at high risk of prostate cancer metastasis or recurrence, even with negative conventional imaging studies.